Data Published From Major-Bleeding Subanalysis of AMPLIFY Trial of Eliquis

December 11, 2015—Bristol-Myers Squibb Company and Pfizer Inc. announced results from a post-hoc early time course subanalysis of the phase 3 AMPLIFY trial. The subanalysis data were published by Gary E. Raskob, PhD, et al in Thrombosis and Haemostasis.

The subanalysis demonstrated that the companies’ Eliquis (apixaban, an oral selective Factor Xa inhibitor) was comparable to conventional therapy (subcutaneous enoxaparin overlapped and followed by oral warfarin dose-adjusted to an international normalized ratio of 2–3) in recurrent VTE and VTE-related death with significantly less major bleeding during the first 7, 21, and 90 days after starting treatment. 

According to the companies, the results of the subanalyses at each prespecified time interval were consistent with the overall results of the AMPLIFY trial at 6 months, which demonstrated noninferiority of Eliquis versus conventional therapy in the primary efficacy endpoint of recurrent VTE and VTE-related death. The subanalysis demonstrated superiority in the primary safety endpoint with significantly fewer major bleeding events, with a 69% relative risk reduction (absolute risk reduction of 1.1 percentage points [95% confidence interval, -1.7 to -0.6]) compared to conventional therapy.

In this post-hoc early time course subanalysis, recurrent VTE and VTE-related death at 7, 21, and 90 days after starting treatment occurred in 18 (0.7%), 29 (1.1%), and 46 (1.8%) patients who were given Eliquis, respectively, and in 23 (0.9%), 35 (1.3%), and 58 (2.2%) patients given conventional therapy, respectively. 

Outcomes at each time point were similar in patients by index event (DVT alone or PE with or without DVT) and were consistent with the results for the entire study period. Major bleeding at the corresponding time points occurred in 3 (0.1%), 5 (0.2%), and 11 (0.4%) patients, who received Eliquis, respectively, and in 16 (0.6%), 26 (1.0%), and 38 (1.4%) patients given conventional therapy, respectively. Eliquis was noninferior to conventional therapy in recurrent VTE and VTE-related death at each time point analyzed, with no excess of early recurrences; and patients treated with Eliquis were less likely to have major bleeding early in the course of treatment than those treated with conventional therapy, reported Bristol-Myers Squibb and Pfizer.

In the companies’ press release, AMPLIFY steering committee chair, Giancarlo Agnelli, MD, commented, “For the millions of patients worldwide who experience VTE, the risks of recurrence and major bleeding are highest during the first few weeks of anticoagulant therapy. These findings indicate that the favorable benefit-to-risk profile of Eliquis was demonstrated early during treatment for VTE, including the use of a higher Eliquis dose of 10 mg twice daily for the initial 7 days.” Dr. Agnelli is professor of internal medicine at the University of Perugia, Italy, and Director of the department of internal and cardiovascular medicine and stroke-unit at the University Hospital in Perugia, Italy.